Unexpected Effects of Epitope and Chimeric Tags on Gonadotropin-Releasing Hormone Receptors: Implications for Understanding the Molecular Etiology of Hypogonadotropic Hypogonadism

Shaun P. Brothers, Jo Ann Janovick, P. Michael Conn

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations

Abstract

In the case of human GnRH receptor (GnRHR) mutants associated with hypogonadotropic hypogonadism, a view emerged that these mutants are correctly routed to the plasma membrane. This view, supported almost entirely by studies using the HA-tag (hemagglutinin influenza virus epitope tag) and other epitope and chimeric tags, obscured recognition that GnRHR mutants frequently become misrouted proteins. The underlying assumption in epitope and chimeric tagging studies is that the cell does not distinguish tagged from unmodified proteins. It should not have been surprising, in retrospect, to find that even a single amino acid mutation dramatically alters protein function or routing because increased plasma membrane expression is associated with deletion of a single amino acid in the human GnRHR (K191), and point mutations have been shown to block plasma membrane routing of many receptors, including most of those responsible for the hypogonadotropic hypogonadism phenotype. Our present observations suggest that epitope and chimeric tags do have a significant effect on protein localization and function. Although rarely provided, control experiments addressing the effects of epitope or chimeric tagging are an essential part of any study relying on these proteomic tools.

Original languageEnglish (US)
Pages (from-to)6107-6112
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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